Nomogram models for predicting overall and cancer-specific survival in early-onset gastric cancer patients: a population-based cohort study.

To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.

CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men.

Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT-like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head-tail coupling apparatus in the sperm of Ccdc157-null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157-deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.

Splicing Mutation in DNALI1 Causes Male Infertility with Severe Oligoasthenoteratozoospermia in Humans.

Oligo-astheno-teratozoospermia (OAT), which is a common cause of male infertility, can be caused by genetic factors. This study reports on a case of a male patient suffering from infertility concomitant with OAT. Whole-exome sequencing (WES) confirmed the presence of a homozygous variant (NM_003462: c.464-1G > A) in the DNALI1 gene via Sanger sequencing. Immunofluorescence staining demonstrated that the DNALI1 signal was nearly undetectable in the patient's sperm. Bioinformatics analysis revealed that this mutation could reverse the splicing of the exon 4 acceptor splice site. A minigene experiment was performed to verify the mutation and the results confirmed that the mutation disrupted the splicing. Our findings show that this rare mutation in DNALI1 contributes to male infertility and OAT in humans, thereby expanding our understanding of the causes and pathogenesis of male infertility. This knowledge facilitates genetic counseling, clinical diagnosis, and therapeutic development of male infertility.

Y chromosome polymorphisms contribute to an increased risk of non-obstructive azoospermia: a retrospective study of 32,055 Chinese men.

PURPOSE: To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes. METHODS: The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes. RESULTS: The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528). CONCLUSIONS: Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.

Pseudo anomalies enhanced deep support vector data description for electrocardiogram quality assessment.

Electrocardiogram (ECG) recordings obtained from wearable devices are susceptible to noise interference that degrades the signal quality. Traditional methods for assessing the quality of electrocardiogram signals (SQA) are mostly supervised and typically rely on limited types of noise in the training data, which imposes limitations in detecting unknown anomalies. The high variability of both ECG signals and noise presents a greater challenge to the generalization of traditional methods. In this paper, we propose a simple and effective unsupervised SQA method by modeling the SQA of ECG as a problem of anomaly detection, in which, a model of pseudo anomalies enhanced deep support vector data description is introduced to learn a more discriminative and generalized hypersphere of the high-quality ECG in a self-supervised manner. Specifically, we propose a series of ECG noise-generation methods to simulate the noise of real scenarios and use the generated noise samples as the pseudo anomalies to correct the hypersphere learned solely by the high-quality ECG samples. Finally, the quality of ECG can be measured based on the distance to the center of the hypersphere. Extensive experimental results on multiple public datasets and our constructed real-world 12-lead dataset demonstrate the effectiveness of the proposed method.

Re-assessment of the close relationship between serum FSH levels and semen quality: a retrospective cohort study of 11,929 Chinese men.

PURPOSE: To establish a medically valuable normal reference interval of follicle-stimulating hormone (FSH) levels in males with normal semen and to assess the predictive value of FSH in males exhibiting semen abnormalities. METHODS: The study involved male patients who underwent their initial serum sex hormone test and semen test between October 2013 and June 2023. The reference interval was identified as the 95% confidence interval (CI) of FSH values in the patients with normal semen parameters. Then, in the total study population, receiver operating characteristic (ROC) curves were performed to evaluate the discriminatory ability of FSH for oligozoospermia and non-obstructive azoospermia (NOA). Besides, multivariable logistic regression was performed to investigate the association of FSH with oligozoospermia and NOA adjusted by age. RESULTS: A total of 11,929 patients were finally enrolled in the study. The normal reference interval of FSH ranged from 1.70 IU/L to 7.60 IU/L (median: 3.98 IU/L) based on 4595 patients with normal semen routine parameters. In the total patients, ROC curves showed FSH to have a "fair" discriminatory ability for oligozoospermia (area under receiver operating characteristic curve (AUC) 0.747, threshold 7.32 IU/L, accuracy 0.734, positive predictive value (PPV) 0.754, negative predictive value (NPV) 0.726), while ROC curves showed FSH to have a "excellent" discriminatory ability for NOA (AUC: 0.921, threshold 10.18 IU/L, accuracy 0.903, PPV 0.593, NPV 0.972). Besides, multivariable logistic regression showed that FSH ≥ 7.32 IU/L was associated with a 8.51-fold increase in the risk of oligozoospermia adjusted by age, while FSH ≥ 10.18 IU/L was associated with a 38.93-fold increase in the risk of NOA. CONCLUSIONS: Our findings indicated that the reference interval for FSH in males with normal semen was 1.70-7.60 IU/L and found that FSH was capable of effectively discerning oligospermia and NOA.

Spleen Thickness Plus Platelets Can Effectively and Safely Screen for High-Risk Varices in Cirrhosis Patients.

Currently, most primary hospitals cannot routinely perform liver stiffness measurements (LSMs) and spleen stiffness measurements (SSMs), which are recommended by guidelines to exclude high-risk varices (HRVs). We tried to find more convenient indicators for HRV screening. We enrolled 213 cirrhosis patients as the training cohort (TC) and 65 primary biliary cirrhosis patients as the validation cohort (VC). We included indicators such as SSM by two-dimensional shear wave elastography, LSM by transient elastography, and other imaging and laboratory tests. Variable analysis revealed SSM, platelets (PLT), and spleen thickness (ST) as independent risk indicators for HRV. In TC, ST+PLT (ST < 42.2 mm and PLT > 113.5 × 109/L) could avoid 35.7% of the esophagogastroduodenoscopies (EGDs), with a 2.4% missed HRV rate. Although the proportion of EGDs spared by ST+PLT was less than SSM+PLT (SSM < 29.89 kPa + PLT > 113.5 × 109/L) (35.7% vs. 44.1%), it was higher than that of the Baveno VI criteria (B6) (35.7% vs. 28.2%). We did not validate SSM+PLT in VC considering our aims. ST+PLT safely spared 24.6% of EGDs in VC, identical to B6. Conclusions: The ability of ST+PLT to exclude HRVs was superior to B6 but slightly inferior to SSM+PLT. When SSM cannot be routinely performed, ST+PLT provides an extra option for patients to exclude HRVs as a more convenient model.

X-linked RBBP7 mutation causes maturation arrest and testicular tumors.

Maturation arrest (MA) is a subtype of non-obstructive azoospermia, and male infertility is a known risk factor for testicular tumors. However, the genetic basis for many affected individuals remains unknown. Here, we identified a deleterious hemizygous variant of X-linked retinoblastoma-binding protein 7 (RBBP7) as a potential key cause of MA, which was also found to be associated with the development of Leydig cell tumors. This mutation resulted in premature protein translation termination, affecting the sixth WD40 domain of the RBBP7 and the interaction of the mutated RBBP7 with histone H4. Decreased BRCA1 and increased γH2AX were observed in the proband. In mouse spermatogonial and pachytene spermatocyte-derived cells, deprivation of rbbp7 led to cell cycle arrest and apoptosis. In Drosophila, knockdown of RBBP7/Caf1-55 in germ cells resulted in complete absence of germ cells and reduced testis size, whereas knockdown of RBBP7/Caf1-55 in cyst cells resulted in hyperproliferative testicular cells. Interestingly, male infertility caused by Caf1-55 deficiency was rescued by ectopic expression of wild-type human RBBP7 but not mutant variants, suggesting the importance of RBBP7 in spermatogenesis. Our study provides insights into the mechanisms underlying the co-occurrence of MA and testicular tumors and may pave the way for innovative genetic diagnostics of these 2 diseases.

Young patients show poor efficacy for immune checkpoint inhibitor combined therapy in metastatic gastrointestinal cancers.

Background: The impact of age on the efficacy and safety of immunotherapy remains controversial. The previous studies simply classified patients into younger and older groups, which might not reflect the real impact of young age on immunotherapy efficacy. The current study aimed to explore the efficacy and safety of immune checkpoint inhibitor (ICI) combined therapy in young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) patients with metastatic gastrointestinal cancers (GICs), and further determine the role of immunotherapy in young patients. Methods: Patients with metastatic GIC including esophageal cancer (EC), gastric cancer (GC), hepatocellular cancer (HCC), and biliary tract cancer (BTC) who received ICI combination therapy were enrolled, divided into young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups. The clinical characteristics, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared among three groups. Results: A total of 254 patients were finally included, with 18, 139, and 97 cases in the young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups, respectively. Compared to middle-aged and old patients, young patients had lower DCR (all p < 0.05) and also had inferior PFS (p < 0.001) and OS (p = 0.017). The multivariate analyses showed that young age was an independent prognostic factor for PFS [hazard ratio (HR) 3.474, 95% confidence interval (CI) 1.962-6.150, p < 0.001] and OS (HR 2.740, 95% CI 1.348-5.570, p = 0.005). Subsequent safety analyses referring to irAEs demonstrated no significant differences for distribution frequency among each age group (all p > 0.05), whereas patients with irAEs displayed better DCR (p = 0.035) and PFS (p = 0.037). Conclusion: Younger GIC patients (aged 18-44 years) showed poor efficacy for ICI combined therapy, and irAEs could be used as a clinical biomarker to predict ICI efficacy in metastatic GIC patients.

Morphine poisoning in a patient with malignant peritoneal mesothelioma: A case report.

Pain is one of the most common symptoms of malignant peritoneal mesothelioma. Therefore, analgesia serves an indispensable role in the treatment of this condition. Morphine is a representative opioid, which is widely used in clinical practice; however, excessive or unreasonable application can cause poisoning. Few cases of morphine poisoning have been reported, and cases of morphine poisoning in patients with malignant peritoneal mesothelioma are even more rare. Here, we present a case of morphine poisoning in a patient with malignant peritoneal mesothelioma. The patient had a high abdominal tumor load, hepatorenal insufficiency, and was treated with a combination of morphine and the sedative benzodiazepine, eventually leading to morphine poisoning. Therefore, for cancer pain, omni-directional and whole-process management should be emphasized. In patients with hepatorenal insufficiency, those treated with morphine combined with benzodiazepines, or those with a high abdominal tumor load, attention should be paid to drug absorption, excretion and interaction, and the drug dose during administration should be reduced to avoid drug poisoning. If poisoning symptoms occur, timely measures should be taken to reduce poison absorption and increase poison excretion, and antagonists should be used to reverse the poisoning and reduce the damage caused.

Effects of major depression and bipolar disorder on erectile dysfunction: a two-sample mendelian randomization study.

BACKGROUND AND AIMS: There are currently no clear conclusions about whether major depression (MD) and bipolar disorder (BD) increase the risk of erectile dysfunction (ED). In our study, we used a Mendelian randomization (MR) analysis to discover the causal associations between MD, BD and ED. METHODS: We got single-nucleotide polymorphisms (SNPs) related to MD, BD and ED from the MRC IEU Open genome-wide association study (GWAS) datasets. After a series of selection, SNPs left were selected as instrumental variables (IVs) of MD and BD for the following MR test to evaluate the relationship of genetically predicted MD or BD with the incidence of ED. Among them, we used the random-effects inverse-variance weighted (IVW) method as the main analysis. Finally, sensitivity analyses were further performed using Cochran's Q test, funnel plots, MR-Egger regression, Leave-one-out method and MR- pleiotropy residual sum and outlier (PRESSO). RESULTS: Genetically-predicted MD was causally related to the incidence of ED in the IVW methods (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.19-1.96; p = 0.001), while no causal impact of BD on the risk of ED (OR = 0.95, 95% CI 0.87-1.04; p = 0.306). The results of sensitivity analyses supported our conclusion, and no directional pleiotropy were found. CONCLUSION: The findings of this research found evidence of a causal relationship between MD and ED. However, we did not find a causal relationship between BD and ED in European populations.

Genome-wide analysis of MYB family in Nicotiana benthamiana and the functional role of the key members in resistance to Bemisia tabaci.

MYB transcription factors (TFs) play a key role in plant resistance to abiotic and biotical stresses. However, little is currently known about their involvement in the plant defense to piercing-sucking insects. Here, we studied the MYB TFs that responded to and resisted Bemisia tabaci whitefly in the model plant Nicotiana benthamiana. Firstly, a total of 453 NbMYB TFs in N. benthamiana genome were identified and 182 R2R3-MYB TFs were analyzed for molecular characteristics, phylogenetic analysis, genetic structure, motif composition, and cis-elements. Then, six stress-related NbMYB genes were selected for further study. The expression pattern shows they were highly expressed in mature leaves and intensively induced upon whitefly attack. Combined with bioinformatic analysis, overexpression, ß-Glucuronidase (GUS) assay, and virus-induced silencing tests, we determined the transcriptional regulation of these NbMYBs on the genes in lignin biosynthesis and SA-signaling pathways. Meanwhile, we tested the performance of whitefly on plants with increased or silenced NbMYB genes expression and found that NbMYB42, NbMYB107, NbMYB163, and NbMYB423 were resistant to whitefly. Our results contribute to a comprehensive understanding of the MYB TFs in N. benthamiana. Furthermore, our findings will facilitate further studies on the role of MYB TFs in the interaction between plants and piercing-sucking insects.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review.

Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

A molecular classification of gastric cancer associated with distinct clinical outcomes and validated by an XGBoost-based prediction model.

Gastric cancer (GC) is a heterogeneous disease and a leading cause of cancer-related deaths. Discovering robust, clinically relevant molecular classifications is critical for guiding personalized therapies for GC. Here, we propose a refined molecular classification scheme for GC using integrated optimal algorithms and multi-omics data. Based on the important features of mRNA, microRNA, and DNA methylation data selected by the multivariate Cox regression model, three subtypes linked to distinct clinical outcomes were identified by combining similarity network fusion and consensus clustering methods. Three subtypes were validated by an extreme gradient boosting machine learning prediction model with 125 differentially expressed genes in multiple independent cohorts. The molecular characteristics of mutation signatures, characteristic gene sets, driver genes, and chemotherapy sensitivity for each subtype were also identified: subtype 1 was associated with favorable prognosis and characterized by high ARID1A and PIK3CA mutations, subtype 2 was associated with a poor prognosis and harbored high recurrent TP53 mutations, and subtype 3 was associated with high CHD1, APOA1 mutations, and a poor prognosis. The proposed three-subtype scheme achieved a better clinical prediction performance (area under the curve value = 0.71) than The Cancer Genome Atlas classification, which may provide a practical subtyping framework to improve the treatment of GC.

Targeted therapy for multiple gene mutations in multiple metastases of advanced gastric cancer: a case report.

In China, gastric cancer is the second most common cause of cancer-related death, after lung cancer. At present, the morbidity and mortality rates of gastric cancer are increasing, and targeted therapy for gastric cancer has become a research hotspot. Herein, we report a patient with multiple metastases from advanced gastric cancer. After identifying MET gene amplification, initial treatment induced regression of the tumor. However, in later stages, due to the overexpression or mutation of HER-2, KRAS, TP53, and other genes, the targeted drug therapy became ineffective, and the disease progressed rapidly, leading to the death of the patient.

Characteristics of circadian rhythm-related genes and establishment of a prognostic scoring system for lung adenocarcinoma with experimental verification: a bioinformatics analysis.

Background: Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Lung adenocarcinoma (LUAD), the main subtype of NSCLC, has a poor prognosis. In recent years, circadian rhythm (CR)-related genes (CRRGs) have demonstrated associations with tumor occurrence and development, but the relationship between CRRGs and LUAD is not clear. Because of the correlation between CRRGs and tumors, we have reason to believe that CRRGs will become an important prognostic indicator for LUAD and guide the treatment of LUAD prognosis. Methods: Based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we explored the biological function and immune cell infiltration of LUAD in different CR clusters and quantified CR genes using principal component analysis (PCA). Then, we built a CR scoring system (CRscore) to explore the relationship between CRRGs and LUAD prognosis. Results: Patients were divided into three clusters (A, B, and C). Biological characteristics, such as survival, immune cell infiltration, and gene enrichment, were significantly different among the three clusters (P<0.001). We then established the usefulness of the CR score, which could probably predict the prognosis of LUAD. Specifically, patients with a high CR score had a better prognosis and were more sensitive to chemotherapy than those with a low CR score. Conclusions: It is possible to use CRRGs to assess the prognosis of patients with LUAD. Quantification of CR using the CRscore tool in patients with LUAD maybe help to guide personalized cancer immunotherapy strategies in the future. Thus, the CRscore may be a prognostic tool for LUAD.

Gynecological Diagnosis and Treatment of Ectopic Ureter Insertion into Vagina: Analysis of Five Cases and a Literature Review.

An ectopic ureter is a ureter that does not correctly connect to the trigone of the bladder and drains outside of the bladder. Here, we presented five cases of ectopic ureter opening into the vagina, whose clinical symptoms and malformations were rarely described in previous case reports. All five patients were hospitalized with complaints of gynecologic disease. Three of the five cases did not present the typical symptoms of urinary incontinence. Three of these cases showed congenital malformations of the female genital tract. Four cases were diagnosed in adulthood. All patients were analyzed using various imaging examinations. This study suggests that the ectopic ureter should be considered in the differential diagnosis of a pelvic mass in a patient with urinary and reproductive system abnormalities. It is essential to comprehensively evaluate complex malformations of the genitourinary system with multiple imaging tests.

Regulator of G-protein signaling 1 promotes choroidal neovascularization in age-related macular degeneration.

Background: Age-related macular degeneration (AMD) is the leading cause of blindness, and is associated with oxidative stress and the development of new blood vessels. At present, the main clinical treatment for AMD includes intraocular injection of vascular endothelial growth factor (VEGF). However, treatment includes repeated injections with significant side-effects. Therefore, new treatment options are required. The aim of the present study was to discover the new treatment target of AMD from the gene level. Methods: The Gene Expression Omnibus (GEO) database was used to analyze the differential gene expression in AMD, and the regulator of G-protein signaling 1 (RGS1) was obtained by bioassay. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression levels of RGS1, VEGF, and other related molecules in human microvascular endothelial cells (HMECs) under different conditions. Cell viability, apoptosis, and proliferation of HMECs were measured by Cell Counting Kit-8 proliferation assay. Immunofluorescence and immunohistochemistry detected the interaction between RGS1, platelet endothelial cell adhesion molecule-1, and VEGF. Results: RGS1 was found to closely associated with the proliferation of vascular endothelial cells, and therefore, with angiogenesis. The expression of RGS1, VEGF, and platelet endothelial cell adhesion molecule-1 was upregulated in laser model mice and hypoxia model HMECs. Knockout of RGS1 inhibits the expression of VEGF and HMEC proliferation, thereby inhibiting AMD angiogenesis. Conclusions: Our results support the use of RGS1 as a new potential target for the future treatment of AMD.

Clinical course and management of insidious adrenal crisis manifested initially as hyperpyrexia secondary to pembrolizumab: Case reports and literature review.

Immune checkpoint inhibitors (ICIs) are novel drugs with a dramatic survival benefit in patients with advanced malignancies. With the widespread use, several immune-related adverse events (irAEs) have emerged, which may be life-threatening. Herein we report two patients with adrenal crisis who received anti-programmed cell death protein 1 (PD-1) (pembrolizumab) therapy. Several reports of secondary adrenal insufficiency caused by pembrolizumab exist, including during treatment or late onset. Severe adrenal insufficiency according to the Common Terminology Criteria for Adverse Events (CTCAE) has rarely been described in the literature, since it initially manifests as high-grade fever. The two male patients developed adrenal crisis that was first characterized by hyperpyrexia accompanied by abdominal symptoms. These initial manifestations confused the clinicians who misdiagnosed them as infection. Timely identification, hydrocortisone pulse therapy, and fluid resuscitation improved the patients' condition. Compliance with the standardized treatment approach and course can prevent or relieve the crisis as soon as possible. Assessment of relevant laboratory test results and patient education, including when to use stress-dose hydrocortisone and guidance on route of administration, can reduce the incidence of adrenal crisis. We report these two cases and have evaluated the literature on previously reported cases to improve our understanding of this condition and offer a more scientific approach to diagnosis and treatment options.

Development and validation predictive models of sperm retrieval for azoospermic men undergoing testicular sperm aspiration: a multicentre, retrospective, cohort study.

PURPOSE: Testicular sperm aspiration (TESA) is widely used to retrieve sperm from testis. Diagnostic testicular biopsy should not be routinely performed for azoospermia. Therefore, a good predictive model is needed before TESA. METHODS: A total of 1972 azoospermia patients constituted the modelling set, and 260 azoospermia patients from two other centres constituted the validation set. An integrated predictive model was built using logistic regression. Receiver operating characteristic (ROC), calibration and decision curve analyses were performed to evaluate the performance of follicle-stimulating hormone (FSH), semen volume, testicular volume and the integrated model. RESULTS: The FSH level was the best univariate predictor for successful sperm retrieval (SSR) and was better than semen volume and testicular volume alone (p<0.001, threshold 6.17 IU/L, modelling set area under receiver operating characteristic curve (AUC) 0.80, accuracy 0.79; validation set AUC 0.87, accuracy 0.78). The integrated predictive model had excellent accuracy for predicting SSR (modelling set: AUC 0.93, accuracy 0.89; validation set: AUC 0.96, accuracy: 0.89). Calibration curve analysis indicated that the integrated model calibration was good and better than that of FSH, semen volume and testicular volume alone. Decision curve analysis indicated with a threshold probability between 0.05 and 0.98, the integrated model added more benefit than treating either all or no patients. CONCLUSIONS: The integrated model has excellent discrimination and good calibration. It can help azoospermic men make better decisions before TESA. It should be noted that TESA is not the first-line treatment for non-obstructive azoospermia because of a low sperm retrieval rate.